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Abstract Thanks to the success of deep learning over the past few years, the video person re-identification (ReID) algorithms have achieved high accuracy on multiple public benchmark datasets. However, the available video person ReID datasets cover a limited range of real-world scenarios, and they have several obvious limitations: limited camera viewing angles, tiny variations of the shooting scene, and even errors in manual labels. These disadvantages prevent video person ReID from being widely used in real-life scenarios. In this work, a new high-quality multi-situation video person ReID dataset, named MSA-BUPT, is built to promote the video person ReID task in large-scale urban surveillance. Specifically, MSA-BUPT contains 684 identities, 2,665 trajectories, and nearly 250,000 frames from 200-h videos across various complex scenarios. Person attribute annotations and unannotated video data are also provided for other research perspectives, such as cross-modality ReID, cross-domain ReID, and so on. Furthermore, two plug-and-play components are used to improve retrieval capabilities: a new scenario-based data augmentation method is proposed to alleviate the person misalignment problem; a re-ranking strategy based on person attribute is applied to make secondary adjustments to the content to the results of the model. The extensive experimental results show that the above methods improve the performance of some representative state-of-the-art models on the new dataset.

Abstract Here we presented an electrophysiological dataset collected from layer V of the primary motor cortex (M1) and the corresponding behavior dataset from normal and hemi-parkinson rats over 5 consecutive weeks. The electrophysiological dataset was constituted by the raw wideband signal, neuronal spikes, and local field potential (LFP) signal. The open-field test was done and recorded to evaluate the behavior variation of rats among the entire experimental cycle. We conducted technical validation of this dataset through sorting the spike data to form action potential waveforms and analyzing the spectral power of LFP data, then based on these findings a closed-loop DBS protocol was developed by the oscillation activity response of M1 LFP signal. Additionally, this protocol was applied to the hemi-parkinson rat for five consecutive days while simultaneously recording the electrophysiological data. This dataset is currently the only publicly available dataset that includes longitudinal closed-loop DBS recordings, which can be utilized to investigate variations of neuronal activity within the M1 following long-term closed-loop DBS, and explore additional reliable biomarkers.

Abstract Background Congenital dislocation of the knee is characterised by excessive knee extension or dislocation and anterior subluxation of the proximal tibia, and this disease can occur independently or coexist with different systemic syndromes. Nevertheless, significant controversy surrounds treating this disease when combined with hip dislocation. This paper presents a case of a 4-month-old patient diagnosed with bilateral hip dislocation combined with this disease. The study discusses the pathophysiology, diagnosis, and treatment methods and reviews relevant literature. Case presentation We reported a case of a 4-month-old female infant with congenital dislocation of the right knee joint, which presented as flexion deformity since birth. Due to limitations in local medical conditions, she did not receive proper and effective diagnosis and treatment. Although the flexion deformity of her right knee joint partially improved without treatment, it did not fully recover to normal. When she was 4 months old, she came to our hospital for consultation, and we found that she also had congenital dislocation of both hip joints and atrial septal defect. We performed staged treatment for her, with the first stage involving surgical intervention and plaster orthosis for her congenital dislocation of the right knee joint, and the second stage involving closed reduction and plaster fixation orthosis for her congenital hip joint dislocation. Currently, the overall treatment outcome is satisfactory, and she is still under follow-up observation. Conclusions Early initiation of treatment is generally advised, as nonsurgical methods prove satisfactory for mild cases. However, surgical intervention should be considered in cases with severe stiffness, unresponsive outcomes to conservative treatment, persistent deformities, or diagnoses and treatments occurring beyond the first month after birth.

In this paper, a novel ultrasonic treatment technique was proposed in nodular cast iron melt with the aim of improving the microstructure and mechanical properties of nodular cast iron. The effects of ultrasound on the microstructures and properties were investigated by comparing experiments with and without ultrasound. The results showed that compared with the NO UT specimen, the mean equivalent diameter of graphite nodules was reduced by 46% in the UT 105 s specimen, while the mean roundness and nodule count per unit area were increased by 33.9% and 43.6%, respectively. In addition, the ultrasonic treatment of melt could increase the pearlite content, refine the matrix microstructure and reduce the pearlite interlamellar spacing from 392.7 nm to 231.3 nm. Compared with the NO UT specimen, the mechanical properties of the UT specimen were improved significantly, and could up to UTS of 739 MPa, YS of 579 MPa and El of 9.4% in the UT 105 s specimen. In this work, the mechanism of ultrasonic action on nodular cast iron also was discussed in detail.

Nongchuangke refers to a new group of professional farmers that promotes agricultural innovation and sustainable development. Here, a comprehensive evaluation system for the livelihood-resilience index of the Nongchuangke in Zhejiang Province was constructed using three parameters: the buffer, self-organization, and learning capacities of the Nongchuangke. The entropy method was employed to comprehensively evaluate the livelihood resilience level of the Nongchuanke in Zhejiang Province, and a decision-making trail and evaluation laboratory with interpretive structural modeling was employed to clarify the hierarchical relationships among the limiting factors of the livelihood resilience of the Nongchuangke in Zhejiang Province and identify the key limiting factors. The results revealed that the average livelihood resilience level of the Nongchuangke in Zhejiang Province was low. Furthermore, the policy support, attraction of entrepreneurial investment, information-acquisition ability, and the number of Nongchuangke per 10,000 farmers were identified as the key factors influencing the livelihood resilience level of Nongchuangke in Zhejiang Province. Thus, new approaches that improve the identified influencing factors must be considered and implemented to improve the livelihood resilience level of the Nongchuangke.

Background: Accumulating evidence has shown that circular RNAs (circRNAs) are involved in gastric cancer (GC) tumorigenesis. However, specific functional circRNAs in GC remain to be discovered, and their underlying mechanisms remain to be elucidated. Methods: CircRNAs that were differentially expressed between GC tissues and controls were analyzed using a circRNA microarray dataset. The expression of circVDAC3 in GC was determined using quantitative real-time PCR (qRT-PCR), and the structural features of circVDAC3 were validated. Cell function assays and animal experiments were conducted to explore the effects of circVDAC3 on GC. Finally, bioinformatics analysis, fluorescent in situ hybridization, and dual luciferase assays were used to analyze the downstream mechanisms of circVDAC3. Results: Our results showed that circVDAC3 was downregulated in GC and inhibited the proliferation and metastasis of GC cells. Mechanistically, circVDAC3 acts as a competing endogenous RNA (ceRNA) of miR-592 and deregulates the repression of EIF4E3 by miR-592. EIF4E3 is downregulated in GC and overexpression of miR-592 or knockdown of EIF4E3 in circVDAC3-overexpressing cells weakens the anticancer effect of circVDAC3. Conclusion: Our study provides evidence that circVDAC3 affects the growth and metastasis of GC cells via the circVDAC3/miR-592/EIF4E3 axis. Our findings offer valuable insights into the mechanisms underlying GC tumorigenesis and suggest novel therapeutic strategies.

Abstract Background Type 1 gastric neuroendocrine tumors (NETs) are relatively rare to the extent that some physicians have little experience in diagnosing and treating them. The purpose of this study was to increase the understanding of the disease by analyzing and summarizing the management and prognoses of patients with type 1 gastric NETs at our center. Methods The data of 229 patients (59.4% female) with type 1 gastric NETs who were treated at our center during 2011–2022 were retrospectively analyzed. Results The average patient age was 50.5 ± 10.8 years. Multiple tumors affected 72.5% of the patients; 66.4% of the tumors were

Summary: B7-H3 is a common oncogene found in various cancer types. However, the molecular mechanisms underlying abnormal B7-H3 expression and colorectal cancer (CRC) progression need to be extensively explored. B7-H3 was upregulated in human CRC tissues and its abnormal expression was correlated with a poor prognosis in CRC patients. Notably, gain- and loss-of-function experiments revealed that B7-H3 knockdown substantially inhibited cell proliferation, migration, and invasion in vitro, whereas exogenous B7-H3 expression yielded contrasting results. In addition, silencing of B7-H3 inhibited tumor growth in a xenograft mouse model. Mechanistically, our study demonstrated that the N6-methyladenosine (m6A) binding protein YTHDF1 augmented B7-H3 expression in an m6A-dependent manner. Furthermore, rescue experiments demonstrated that reintroduction of B7-H3 considerably abolished the inhibitory effects on cell proliferation and invasion induced by silencing YTHDF1. Our results suggest that the YTHDF1-m6A-B7-H3 axis is crucial for CRC development and progression and may represent a potential therapeutic target for CRC treatment.

Ectopic adrenocorticotropic hormone syndrome (EAS) is a rare condition caused by pancreatic neuroendocrine tumors (p-NETs). The severe hypercortisolemia that characterizes EAS is associated with a poor prognosis and survival. Mitotane is the only adrenolytic drug approved by the Food and Drug Administration and is often used to treat adrenocortical carcinoma. Combination therapy with mitotane and other adrenal steroidogenesis inhibitors is common for patients with Cushing’s syndrome (CS). Here, we describe three patients who developed EAS secondary to the liver metastasis of p-NETs. All three rapidly developed hypercortisolemia but no typical features of CS. They underwent anti-tumor and mitotane therapy, which rapidly reduced their blood cortisol concentrations and ameliorated their symptoms. Their hypercortisolemia was controlled long term using a low dose of mitotane. The principal adverse effects were a slight loss of appetite and occasional dizziness, and there were no severe adverse effects. Importantly, even when the tumor progressed, the patients’ circulating cortisol concentrations remained within the normal range. In summary, the present case series suggests that mitotane could be used to treat hypercortisolemia in patients with EAS caused by advanced p-NETs, in the absence of significant adverse effects.

AbstractThe increase in the number and severity of seismic disasters has put communities in danger, especially in rapidly developing and densely populated areas. Traditional seismic vulnerability and risk assessment methods, including field investigation, are accurate at the building scale; however, their low-efficiency and high-cost characteristics limit the application of these methods in urban-scale regions with high-speed development and risk exposure. To address this issue, multisource remote sensing interpretation, support vector machine (SVM) and geographic information science (GIScience) technologies are combined to test the performance and efficiency of a urban-scale macroscopic seismic vulnerability and risk assessment method in the Lixia District of Jinan City, Shandong Province, China, which is characterized by rapid development, a variety of building types, and moderate-to-low seismic risk. First, a traditional field survey was conducted in Lixia District, and a building attribute information database was constructed. Second, the vulnerability proxies of building attribute information and building seismic vulnerability were estimated based on the EMS-98 standard and the SVM. Finally, vulnerability proxies established based on the RISK-UE model were applied to the Lixia database, and the vulnerability and risk assessment under different seismic intensities were estimated with the experimental accuracy verified. The results showed that the SVM method can obtain stable and accurate results in urban scale vulnerability assessment. The mean building vulnerability index in Lixia District is 0.43, which indicates that the overall seismic performance is good. Most of the area falls within the seismic intensity range of VII-X degrees and would experience slight to moderate damage. The results of the study contribute to enhancing the precision and efficacy of large-scale seismic risk assessment, and they can be used by relevant departments to create tailored emergency plans and reduce seismic hazard losses. Additionally, these results can aid in achieving the climate action goal (SDG13) of the United Nations Sustainable Development Goals (SDGs).

AbstractPurpose To determine the effects of tract embolization with gelatin sponge particles on the prevention of pneumothorax after percutaneous microwave ablation (MWA) in rabbit lungs.Materials and methods Twenty-four New Zealand white rabbits were randomly divided into Group A (MWA followed by tract embolization with gelatin sponge particles, n = 12) and Group B (MWA without tract embolization, n = 12). For each group, CT images were reviewed for the occurrence of pneumothorax within 30 min after MWA. The rate of pneumothorax was compared by Chi-square Test. Lung tissue around the needle tract was harvested after the rabbits were euthanized, and histopathological examinations were performed and studied with hematoxylin and eosin stains.Results Twenty-four animals underwent 47 sessions of MWA (24 sessions in Group A and 23 sessions in Group B). Group A had a statistically lower rate of pneumothorax than Group B (25.0 vs. 56.5%; p = 0.028). The pathological examinations of both groups demonstrated thermal injury of the needle tract characterized by a rim of the coagulated lung parenchyma, which might be responsible for pneumothorax after MWA. Gelatin sponge particles could be arranged in irregular flakes densely to effectively seal the needle tract, thus reducing the occurrence of pneumothorax. The gelatin sponge particles could be almost completely absorbed about 14 days later.Conclusion Results of the present study showed needle tract embolization with gelatin sponge particles after CT-guided pulmonary MWA can significantly reduce the incidence of pneumothorax. Gelatin sponge particles can effectively seal the needle tract after ablation and can be completely absorbed in the body with good safety.

Abstract Purpose The role and mechanism of zinc finger DHHC protein 11B (ZDHHC11B) in lung adenocarcinoma (LUAD) remain unclear. We, thus, analyzed the expression pattern, biological function, and potential mechanism of ZDHHC11B in LUAD. Methods The expression level and prognostic value of ZDHHC11B were evaluated based on The Cancer Genome Atlas (TCGA) database and further confirmed in LUAD tissues and cells. The effect of ZDHHC11B on the malignant biological progression of LUAD was evaluated in vitro and in vivo. Gene set enrichment analysis (GSEA) and western blot were used to explore the molecular mechanisms of ZDHHC11B. Results In vitro, ZDHHC11B inhibited the proliferation, migration, and invasion of LUAD cells and induced the apoptosis of LUAD cells. In addition, ZDHHC11B inhibited the growth of tumors in nude mice. GSEA revealed that ZDHHC11B expression is positively correlated with epithelial–mesenchymal transition (EMT). Western blot analysis demonstrated that molecular markers of EMT were inhibited under ZDHHC11B overexpression conditions. Conclusions Our findings indicated that ZDHHC11B plays a significant role in inhibiting tumorigenesis via EMT. In addition, ZDHHC11B may be a candidate molecular target for LUAD treatment.

Abstract Background There is increasing interest in the use of liquid biopsies, but data on longitudinal analyses of circulating tumor DNA (ctDNA) remain relatively limited. Here, we report a longitudinal ctDNA analysis of MONALEESASIA, a phase Ib trial evaluating the efficacy and safety of ribociclib plus endocrine therapy (ET) in Asian patients with hormone receptor–positive, human epidermal growth factor receptor-2–negative advanced breast cancer. Methods MONALEESASIA enrolled premenopausal and postmenopausal Japanese and postmenopausal non-Japanese Asian patients. All patients received ribociclib with ET (letrozole, fulvestrant, or tamoxifen with goserelin). ctDNA was analyzed using a targeted next-generation sequencing panel of 572 cancer-related genes and correlated by best overall response (BOR). Results Five hundred seventy-four cell-free DNA samples from 87 patients were tested. The most frequently altered genes at baseline included PIK3CA (29%) and TP53 (22%). Treatment with ribociclib plus ET decreased ctDNA in most patients at the first on-treatment time point, regardless of dose or ET partner. Patients with partial response and stable disease had lower ctDNA at baseline that remained low until data cutoff if no progressive disease occurred. Most patients with progressive disease as the best response had higher ctDNA at baseline that remained high at the end of treatment. For patients with partial response and stable disease with subsequent progression, ctDNA increased towards the end of treatment in most patients, with a median lead time of 83 days (14–309 days). In some patients with BOR of partial response who experienced disease progression later, specific gene alterations and total ctDNA fraction increased; this was sometimes observed concurrently with the development of new lesions without a change in target lesion size. Patients with alterations in PIK3CA and TP53 at baseline had shorter median progression-free survival compared with patients with wild-type PIK3CA and TP53, 12.7 and 7.3 months vs 19.2 and 19.4 months, respectively (P = .016 and P = .0001, respectively). Conclusions Higher ctDNA levels and PIK3CA and TP53 alterations detected at baseline were associated with inferior outcomes. On-treatment ctDNA levels were associated with different patterns based on BOR. Longitudinal tracking of ctDNA may be useful for monitoring tumor status and detection of alterations with treatment implications. Trial registration ClinicalTrials.gov NCT02333370 . Registered on January 7, 2015.

Abstract Genomically-informed therapy requires consideration of the functional impact of genomic alterations on protein expression and/or function. However, a substantial number of variants are of unknown significance (VUS). The MD Anderson Precision Oncology Decision Support (PODS) team developed an actionability classification scheme that categorizes VUS as either “Unknown” or “Potentially” actionable based on their location within functional domains and/or proximity to known oncogenic variants. We then compared PODS VUS actionability classification with results from a functional genomics platform consisting of mutant generation and cell viability assays. 106 (24%) of 438 VUS in 20 actionable genes were classified as oncogenic in functional assays. Variants categorized by PODS as Potentially actionable (N = 204) were more likely to be oncogenic than those categorized as Unknown (N = 230) (37% vs 13%, p = 4.08e-09). Our results demonstrate that rule-based actionability classification of VUS can identify patients more likely to have actionable variants for consideration with genomically-matched therapy.

Mobile laser scanning (MLS) systems have become an important technology for collecting and measuring road information for highway maintenance and reconstruction services. However, the efficient and accurate extraction of unstructured road surfaces from MLS point cloud data collected on highways is challenging. Specifically, the complex and unstructured characteristics of road surveying point cloud data lead to traditional 3D point cloud segmentation. When traditional 3D point cloud algorithms extract unstructured road surfaces, over-segmentation and under-segmentation often occur, which affects efficiency and accuracy. To solve these problems, this study introduces an enhanced road extraction method that integrates supervoxel and trajectory information into a traditional region growing algorithm. The method involves two main steps: first, a supervoxel data structure is applied to reconstruct the original MLS point cloud data, which diminishes the calculation time of the point cloud feature vector and accelerates the merging speed of a similar region; second, the trajectory information of the vehicle is used to optimize the seed selection strategy of the regio growing algorithm, which improves the accuracy of road surface extraction. Finally, two typical highway section tests (flat road and slope road) were conducted to validate the positioning performance of the proposed algorithm in an MLS point cloud. The results show that, compared with three kinds of traditional road surface segmentation algorithms, our method achieves an average extraction recall and precision of 99.1% and 96.0%, and by calculating the recall and precision, an F1 score of 97.5% can be obtained to evaluate the performance of the proposed method, for both datasets. Additionally, our method exhibits an average road surface extraction time that is 45.0%, 50.3%, and 55.8% faster than those of the other three automated segmentation algorithms.

Tropane alkaloids (TAs) are synthesized by some species in Solanaceae. Here, the authors assemble the genomes of two representative TAs producing species, show that gene loss shapes uneven distribution of TAs in Solanaceae, and identify a cytochrome P450 gene catalyzing N-demethylation of hyoscyamine to generate norhyoscyamine.

Summary: Wiskott–Aldrich syndrome protein-interacting protein family member 1 (WIPF1) is associated with malignant tumor progression. However, molecular links between WIPF1 and gastric cancer (GC) remain elusive. The expression of WIPF1 was detected in GC tissues and cells. WIPF1 was overexpressed in GC tissues and cells and high expression of WIPF1 was an independent risk factor for a poor prognosis in patients with GC. Further experiments indicated that WIPF1 promoted the proliferation, invasion, and migration of GC cells in vivo and in vitro. WIPF1-regulated genes were closely related to cell proliferation and migration in GC, and silencing WIPF1 significantly repressed PI3K/AKT signaling pathway activation. WIPF1 was activated by myocardin (MYOCD) translation. Rescue experiments confirmed that MYOCD promotes the proliferation, invasion, and migration of GC cells in a WIPF1-dependent manner and activates the PI3K/AKT signaling pathway. MYOCD may transactivate WIPF1 and facilitate GC cell growth and metastasis by activating the PI3K/AKT signaling pathway.

Fluorescence microscopy is a powerful tool for scientists to observe the microscopic world, and the fluorescence excitation light source is one of the most critical components. To compensate for the short operation lifetime, integrated light sources, and low excitation efficiency of conventional light sources such as mercury, halogen, and xenon lamps, we designed an LED-integrated excitation cube (LEC) with a decentralized structure and high optical power density. Using a Fresnel lens, the light from the light-emitting diode (LED) was effectively focused within a 15 mm mounting distance to achieve high-efficiency illumination. LEC can be easily designed in the shape of fluorescence filter cubes for installation in commercial fluorescence microscopes. LECs’ optical efficiency is 1–2 orders of magnitude higher than that of mercury lamps; therefore, high-quality fluorescence imaging with spectral coverage from UV to red can be achieved. By replacing conventional fluorescence filter cubes, LEC can be easily installed on any commercial fluorescence microscope. A built-in LEC driver can identify the types of LEDs in different spectral bands to adopt the optimal operating current and frequency of pulses. Moreover, high-contrast images can be achieved in pulse mode by time-gated imaging of long-lifetime luminescence.

Walking detection in the daily life of patients with Parkinson’s disease (PD) is of great significance for tracking the progress of the disease. This study aims to implement an accurate, objective, and passive detection algorithm optimized based on an interpretable deep learning architecture for the daily walking of patients with PD and to explore the most representative spatiotemporal motor features. Five inertial measurement units attached to the wrist, ankle, and waist are used to collect motion data from 100 subjects during a 10-meter walking test. The raw data of each sensor are subjected to the continuous wavelet transform to train the classification model of the constructed 6-channel convolutional neural network (CNN). The results show that the sensor located at the waist has the best classification performance with an accuracy of 98.01%±0.85% and the area under the receiver operating characteristic curve (AUC) of 0.9981±0.0017 under ten-fold cross-validation. The gradient-weighted class activation mapping shows that the feature points with greater contribution to PD were concentrated in the lower frequency band (0.5~3Hz) compared with healthy controls. The visual maps of the 3D CNN show that only three out of the six time series have a greater contribution, which is used as a basis to further optimize the model input, greatly reducing the raw data processing costs (50%) while ensuring its performance (AUC=0.9929±0.0019). To the best of our knowledge, this is the first study to consider the visual interpretation-based optimization of an intelligent classification model in the intelligent diagnosis of PD.

Supervoxels provide a natural and compact representation of 3D point clouds that enables operations to be performed on regions rather than on scattered points. However, most supervoxel segmentation methods generate supervoxels based on geometric dissimilarity among points and cannot preserve accurate structure boundaries when noise and outliers are present due to the uncertainty in the random sampling of representative points (RPs). This paper formulates indoor supervoxel segmentation as selecting RPs and matching each point with its RP simultaneously. The RPs are selected from nonboundary areas instead of randomly sampled points, guaranteeing the correctness of sampling from the same structure. The best point-to-RP matching is achieved through iterative refinement/clustering via an energy descent method, which ensures the optimal overall segmentation. Experimental tests on five publicly available datasets demonstrate that our method preserves indoor structure boundaries and small structures more effectively than other state-of-the-art methods, resulting in performance scores of approximately 0.65 for boundary recall.

The underlying molecular mechanisms of colorectal cancer (CRC) has attracted great attention from the scholarly community. The aim of our study is to identify pivotal genes related to the pathogenesis and prognosis of CRC. We integrated five microarray datasets from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were analyzed with the limma package. DAVID and OmicShare tools were used for Gene Ontology (GO) and KEGG enrichment analysis. The protein–protein interaction (PPI) network of DEGs was constructed. The prognostic analysis of hub genes was performed through Kaplan Meier-plotter. Finally, potential drugs were predicted in the CMap database. Through five microarray datasets, a total of 90 DEGs were detected including 54 up-regulated and 36 down-regulated genes. Biological process analysis showed DEGs were mainly enriched in positive regulation of neutrophil chemotaxis, chemokine-mediated signaling pathway, and bicarbonate transport. Signaling pathway analysis indicated that DEGs played a vital in proximal tubule bicarbonate reclamation, cell cycle and progesterone-mediated oocyte maturation. The GEPIA database confirmed that overexpression levels of hub genes were significantly associated with better survival of patients. Finally, the 20 most significant small molecules were obtained based on the CMap database. Our study has identified novel candidate biomarkers, pathways, and kinases associated with CRC prognosis.

Deep learning-based point cloud semantic segmentation has gained popularity over time, with sparse convolution being the most prominent example. Although sparse convolution is more efficient than regular convolution, it comes with the drawback of sacrificing global context information. To solve this problem, this paper proposes the OcspareNet network, which uses sparse convolution as the backbone and captures global contextual information using the offset attention module and context aggregation module. The offset attention module improves the network’s capacity to obtain global contextual information about the point cloud. The context aggregation module utilizes contextual information in the training and testing phases, which increases the network’s capacity to discern the overall structure and successfully improves the network’s capacity and the accuracy of the difficult-scene segmentation category. Compared to the state-of-the-art (SOTA) models, our model has a smaller parameter count and achieves higher accuracy on challenging segmentation categories such as ‘pictures’, ‘counters’, and ‘desks’ in the ScanNetV2 dataset, with IoU scores of 41.1%, 70.3%, and 72.5%, respectively. Furthermore, ablation experiments confirmed the efficacy of our designed modules.

The nitrogen isotopic compositions of lunar soil have important implications for the sources of lunar volatiles and even the evolution of the moon. At present, the research on the lunar nitrogen isotopic compositions is mainly based on the lunar meteorites and the samples brought back by the Apollo and Luna missions. However, volatiles adsorbed on the surface of the lunar soil may be lost due to changes in temperature and pressure, as well as vibration and shock effects when the sample is returned. At the same time, in the case of low N content in the sample, since N is the main component of the earth’s atmosphere, it is easily affected by the atmosphere during the analysis process. Therefore, in situ nitrogen isotopic analysis of lunar soil on orbit is necessary to avoid the problems mentioned above and is one of the primary science goals for the Lunar Soil Volatile Measuring instrument on Chang’e-7 spacecraft. After the nitrogen purification procedure, the volatiles in lunar soil that are released through single-step or stepped heating techniques diffuse to the quadrupole mass spectrometer to obtain the N contents and isotopic compositions of the lunar soil. This paper introduces the ground test for N isotopic analysis of lunar soil in orbit according to the Lunar Soil Volatile Measuring Instrument. After long-term repeated measurements, the background and CO-corrected Air-STD 14N/15N ratio is 268.986 ± 4.310 (1SD, n = 35), and the overall reproducibility of measurements is 1.6%. The accuracy of N isotopic compositions is calculated to be better than 5%, which can distinguish different sources of N components in lunar soil.

This study examines whether and how risk disclosures in Management Discussion and Analysis (MD&A) affected the stock price crash risk of China’s publicly listed firms over the period of 2017–2021. The empirical results show that risk disclosures within the MD&A section are significantly and negatively associated with the future stock price crash risk, even after controlling for a broad set of well-known factors of crash risk. Additional tests revealed that the impact of MD&A risk disclosures on the stock price crash risk is accentuated when the MD&A disclosure contains more incremental information. The negative association between MD&A risk disclosures and stock price crash risk is also more pronounced for firms with poorer information environments, for firms with weaker external monitoring, and for firms with more investor attention. Our findings are robust to alternative measures of the stock price crash risk, controlling for firm-fixed effects and endogeneity issues, and excluding certain samples. The results indicate that MD&A risk disclosures could help alleviate information asymmetry and mitigate stock price crash risk.

Background: Germline HLA class I molecule supertypes are shown to correlate with response to anti-PD-1 therapy. Here, we investigate the significance of germline HLA-A and HLA-B supertypes in tumour microenvironment of non-small-cell lung cancer. Methods: Totally 278 NSCLC patients were collected retrospectively. HLA genotyping was conducted using next-generation sequencing. The evaluation of tumour-infiltrating lymphocytes was performed by multiplex immunohistochemistry assay. Correlations among HLA supertypes, tumour infiltrating lymphocytes, and clinicopathological characteristics were assessed. Results: HLA-A03 and HLA-B62 were the supertypes with the highest proportions, at 69.1% and 52.2%, respectively. HLA-A02 or HLA-B62, but not HLA-A03, associated with higher PD-L1+ tumour and stromal cells levels, CD68+ cells, and CD68+PD-L1+ cells. Patients with both HLA-A02 and HLA-B62 supertypes displayed significantly higher PD-L1+ cells, CD68+ cells, and CD8+ cells levels than patients with other supertypes (P = 0.0301, P = 0.0479, P = 0.0192). These cells collectively constitute a hot but immunosuppressive tumour microenvironment. Accordingly, patients with both HLA-A02 and HLA-B62 supertypes had short progression-free survival after surgery (HR = 2.27, P = 0.0373). Conclusions: The HLA-A02B62 supertype could serve as a possible indicator of poor prognosis in early-stage lung cancer. However, it may also act as a favorable prognostic factor for immunotherapy, given its association with a PD-L1-positive tumour microenvironment.

Summary: Sequence variation resulting from the evolution of IGH clones and immunophenotypic drift makes it difficult to track abnormal B cells in children with precursor B cell acute lymphoblastic leukemia (pre-B-ALL) by flow cytometry, qPCR, or next-generation sequencing (NGS). The V-(D)-J regions of immunoglobulin and T cell receptor of 47 pre-B-ALL samples were sequenced using the Illumina NovaSeq platform. The IGH rod-like tracer consensus sequence was extracted based on its rod-like alpha-helices structural similarity predicted by AlphaFold2. Additional data from published 203 pre-B-ALL samples were applied for validation. NGS-IGH (+) patients with pre-B-ALL had a poor prognosis. Consistent CDR3-coded protein structures in NGS-IGH (+) samples could be extracted as a potential follow-up marker for pre-B-ALL children during treatment. IGH rod-like tracer from quantitative immune repertoire sequencing may serve as a class of biomarker with significant predictive values for the dynamic monitoring of MRD in pre-B-ALL children.

Abstract The restoration of the normal function of the tumour suppressors, such as p53, is an important strategy in tumour therapeutics. Nonsense-mediated mRNA decay (NMD) inhibition by NMD inhibitor (NMDi) upregulates functional p53 isoforms, p53β and p53γ, and activates the p53 pathway. XR-2, a novel mouse double minute 2 homolog (MDM2) inhibitor, can disrupt the interaction between p53 and MDM2, thus decreasing the MDM2-mediated degradation of p53 and increasing the p53 protein levels. However, the combined effects of these two agents have not been thoroughly explored. This study combined XR-2 and NMDi in four TP53 wild-types and four TP53-mutated cancer cell lines. The combination of these two agents achieved significant synergistic effects on TP53 wild-type cancer cell lines by transactivating p53 target genes, inducing apoptosis, cell-cycle arrest and DNA damage repair. The p53β isoform induced by NMDi enhances the transactivation ability of p53α induced by XR-2, which partially explains the mechanism of the synergistic effects of XR-2 and NMDi. This study identified a combination treatment of NMDi and XR-2 which could serve as a novel cancer therapeutic approach for MDM2-overexpressed TP53 wild-type cancers and delineated a future therapy based on the further reactivation of p53.

ObjectThis study was designed to analyze the cartilaginous predictors of residual acetabular dysplasia (RAD) after early treatment of developmental dysplasia of the hip and their diagnostic accuracy.Study designDatabases such as PubMed, Embase, Cochrane, and Web of science were searched to screen the literature. The quality of the literature was assessed by the QUADAS-2 tool. Qualitative and quantitative synthesis of literature were performed based on extracted data. For quantitative synthesis studies, the sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curve with corresponding confidence intervals were calculated.ResultsFor the cartilaginous acetabular index (CAI) group, the combined values of sensitivity, specificity, and DOR were 0.80 (95% CI = 0.54–0.93), 0.73 (95% CI = 0.57–0.84), and 10.62 (95% CI = 3.96–28.53), respectively. The corresponding values in the cartilaginous center-edge angle (CCE) group were 0.71 (95% CI = 0.57–0.82), 0.78 (95% CI = 0.66–0.87), and 8.64 (95% CI = 3.08–24.25), respectively. The area under the curve (AUC) of SROC was 0.82 (95% CI = 0.78–0.85) and 0.80 (95% CI = 0.76–0.83) for the CAI and CCE groups. The CAI group had higher sensitivity, DOR, and AUC than the CCE group.ConclusionBoth of these two groups have good diagnostic accuracy, and CAI/L-AI has a little edge over CCE/L-CEA. However, there is still more research needed to determine whether they can be used as independent indications for secondary orthopedic surgery.Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier: [CRD42022338332].

PurposeTo explore the characteristics, mechanism, treatment, and prognosis of head–neck separation type of Monteggia equivalent fractures in children.MethodsPatients with this injury were reviewed retrospectively. The lesion was characterized by a fracture of the ulnar with radial neck fracture but without dislocation of the radial head. Our classification was based on the direction of displacement and angulation of fractures on radiographs, divided into the extension-valgus type and flexion-varus type. The fractures were treated with reduction and internal fixation, depending on the fracture type. The clinical results were evaluated by using radiology and the Mayo Elbow Performance Score (MEPS).ResultsA total of 12 patients were followed up for an average of 40.5 months. The ulnar fractures were treated with closed reduction (CR) and K-wire fixation in one patient, elastic stable intramedullary nail (ESIN) fixation in four patients, open reduction (OR) and plate fixation in five, with no fixation in two. CR with ESIN fixation was successful in 11 patients with radial neck fractures, but one underwent OR and K-wire fixation. All fractures healed on time, with fewer complications (avascular necrosis in one patient, and bulk formation of metaphysis in another). The therapeutic efficacy was evaluated by using MEPS and was found to be excellent in 10 patients, good in one, and fair in another.ConclusionsThe head–neck separation type of Monteggia equivalent fractures in children is rare. Its characteristics are different from that of Monteggia fracture. The length and anatomic structure of the ulna should be restored and stabilized first, while the radial neck fracture should be treated with CR and ESIN fixation. Satisfactory clinical results can be achieved with fewer complications.

BackgroundSkeletal maturity can evaluate the growth and development potential of children and provide a guide for the management of adolescent idiopathic scoliosis (AIS). Recent studies have demonstrated the advantages of the Humeral Head Ossification System (HHOS) and the Proximal Femur Maturity Index (PFMI), based on standard scoliosis films, in the management of AIS patients. We further assessed the HHOS and the PFMI method's reliability in the interrater and intrarater.MethodsThe data from 38 patients, including the humeral head and proximal femur on standard scoliosis films, were distributed to the eight raters in the form of a PowerPoint presentation. On 38 independent standard spine radiographs, raters utilized the HHOS and PFMI to assign grades. The PPT sequence was randomly changed and then reevaluated 2 weeks later. For every system, the 95% confidence interval (95% CI) and intraclass correlation coefficient (ICC) were calculated to evaluate the interrater and intrarater reliability.ResultsThe HHOS was extremely reliable, with an intraobserver ICC of 0.802. In the first round, the interobserver ICC reliability for the HHOS was 0.955 (0.929–0.974), while in the second round, it was 0.939 (0.905–0.964). The PFMI was extremely reliable, with an intraobserver ICC of 0.888. In the first round, the interobserver ICC reliability for the PFMI was 0.967 (0.948–0.981), while in the second round, it was 0.973 (0.957–0.984).ConclusionsThe HHOS and PFMI classifications had excellent reliability. These two methods are beneficial to reduce additional exposure to radiation and expense for AIS. There are advantages and disadvantages to each classification. Clinicians should choose a personalized and reasonable method to assess skeletal maturity, which will assist in the management of adolescent scoliosis patients.

Acrylate is a popular polymer grouting material that has been widely used to control groundwater seepage. However, the vulnerability of acrylate slurry to dynamic water washout restricts its application in groundwater environments characterized by high flow velocity and water pressures. In this paper, lithium bentonite (Li-B) was used to modify the traditional magnesium acrylate (AC) grouting material. The influence of Li-B to AC ratios on the modified materials’ washout resistance was explored, and the modification mechanism was analyzed using X-ray diffraction (XRD), infrared spectroscopy (IR), and scanning electron microscopy (SEM). Finally, the anti-washout ability of the modified slurry was verified through engineering applications. Results revealed that LiB-AC grout had adjustable setting times (10.5 to 395.6 s), minimal bleeding (0.1%), higher viscosity (65 mPa·s) and expansibility (350%), stronger anti-water dispersibility (24 times that of pure AC slurry), higher mechanical strength (compressive strength is 0.386 MPa, tensile strength is 0.088 MPa), and better impermeability (2.23 × 10−8 m/s). The lithium bentonite was beneficial to the setting time, bleeding, viscosity, slurry retention rate, impermeability, and mechanical strength of the acrylate grout. However, it diminished the expansibility of the acrylate grout. At the optimal acrylate content (20%), the mechanical strength and impermeability of the LiB-AC grout were the highest. The better performance of LiB-AC grout was attributed to the formation of a more stable and dense interlaced spatial network structure after the modification by Li-B. The LiB-AC grout was used in the dynamic water grouting project of a metro shield tunnel segment and achieved better anti-washout performance than cement-water glass and pure AC slurry.

Abstract Background Extended-spectrum β-lactamases (ESBL)-producing strains of Klebsiella pneumoniae remain a worldwide, critical clinical concern. However, limited information was available concerning ESBL-producing Klebsiella pneumoniae in giant pandas. The objective of this study was to characterize ESBL-producing Klebsiella pneumoniae isolates from captive giant pandas. A total of 211 Klebsiella pneumoniae isolates were collected from 108 giant pandas housed at the Chengdu Research Base of Giant Panda Breeding (CRBGP), China. Samples were screened for the ESBL-producing phenotype via the double-disk synergy test. Result A total of three (1.42%, n = 3/211) ESBL-producing Klebsiella pneumoniae strains were identified, and characterization of ESBL-producing Klebsiella pneumoniae isolates were studied by the detection of ESBL genes and mobile genetic elements (MGEs), evaluation of antimicrobial susceptibility and detection of associated resistance genes. Clonal analysis was performed by multi-locus sequencing type (MLST). Among the three ESBL-producing isolates, different ESBL-encoding genes, including bla CTX-M, and bla TEM, were detected. These three isolates were found to carry MGEs genes (i.e., IS903 and tnpU) and antimicrobial resistance genes (i.e., aac(6')-Ib, aac(6')-I, qnrA, and qnrB). Furthermore, it was found that the three isolates were not hypermucoviscosity, resistant to at least 13 antibiotics and belonged to different ST types (ST37, ST290, and ST2640). Conclusion Effective surveillance and strict infection control strategies should be implemented to prevent outbreaks of ESBL-producing Klebsiella pneumoniae in giant pandas.

Abstract Background Transolecranon fracture-dislocation of the elbow is rarely seen in children. The purpose of this retrospective study was to discuss the pathological characteristics and treatment strategy for this injury in children. Methods From October 2016 to March 2019, 15 patients seen and treated at our institutions for transolecranon fracture-dislocation of the elbow were identified, and their medical records and radiographs were reviewed retrospectively. There were 11 boys and 4 girls, with an average age of 8.3 years (from 5 to 14 years). The left arm was involved in 10 cases, and the right arm was involved in 5 cases. Type I (simple fracture) was found in 11 cases, and type II (comminuted fracture) was found in 4 cases, 3 of which with coronoid process involved. Closed reduction was successful under local anaesthesia in 14 cases but failed in 1 case. In 11 patients with type I fractures, 10 received fixation of Kirschner wire and tension band, and one patient underwent bone plate fixation. In 4 patients with comminuted fractures (type II), internal fixation was performed with Kirschner wires combined with reconstruction plates. Results The 15 patients were followed up for 24 to 48 months (average, 30.2 months). The final evaluation showed fine anatomical relationship of the elbow in all with no complications observed. Failure of internal fixation did not occur in any patient. The fractures acquired bony union in all patients after 8 to 12 weeks (average, 9.6 weeks). The therapeutic efficacy was evaluated at the final follow-up by the Mayo elbow performance score (MEPS) as excellent in 11 cases, good in 3 cases and fair in one case. Conclusions As a type of complicated fracture-dislocation of the elbow, the transolecranon fracture-dislocation is rare in children. The fracture is mainly simple type. Treatment options depend on the type of fracture-dislocation. Only anatomical reduction of the olecranon fracture and restoration of a normal trochlear notch can lead to a stable humeroradial joint and good clinical efficacy.

Once the integrated urban-rural development enters a high-quality development stage, multiple dimensions would be reflected in population, space, economics, society, and environment, which will further advance sustainable development. An integrated urban and rural development have shown different features, rules, and models amid different social systems and in different development stages. Therefore, it's urgent to scientifically measure the integration level of rural and urban areas, revealing the spatial differences, characteristics, and internal mechanism. Targeting the 41 cities within the Yangtze River Delta, this paper evaluates the integrated urban-rural development in this area based on the global principal component analysis, explores its spatial agglomeration and evolution pattern by ESDA method, analyzes the principal factors that result in the spatial differences in integrated urban and rural development in the Yangtze River Delta and their interactive relations by the geographical detector, and discusses the regional differences between those influencing factors by the geographical weighted regression method. The results indicate that (1) the integrated development of the 41 cities is not balanced and there is a great difference between different cities. (2) The integrated development of this area has shown the apparent feature of geographical agglomeration, or in other words, the central cities have become the forces that drive the development of neighboring cities. (3) Since integrated urban-rural development is influenced by economic development, basic infrastructure, government support, and industrial structure, all regions should put forward suggestions for the formulation of policies accordingly based on realities.

Microbiologically induced concrete corrosion (MICC) is a major reason for sewer pipe replacement and rehabilitation. Predicting the depth of concrete corrosion can help make better decisions on the inspection and rehabilitation of pipes. Due to the limited data available, the models using deep learning methods for predicting MICC are prone to overfitting. This study develops an XGBoost-based MICC model with the benefits of hyperparametric auto-optimization. For this purpose, the factors affecting MICC were sorted out to be used as a guide for selecting attributes when building the database. 379 datasets relevant to the corrosion loss of the origin Portland cement-based materials in sewers were collected from literature to establish a database. It is then randomly partitioned into 8:2 training and test datasets. The hyperparameters were adjusted by performing Bayesian optimization for 200 iterations. On the training and test sets, the R2 scores of the trained model are 0.87 and 0.85, respectively. In addition, an ongoing field trail in a sewer well is introduced to test the generalization ability of the model. By deploying the model on the field inspection data, the predicted corrosion loss after 169 days is 1.6 mm, which ranges between 1.5 and 3.5 mm measured. The developed MICC model is anticipated to perform well when fed future inspection data that is richer and more abundant.

In order to reduce the membrane pollution of ultrafiltration caused by natural organic matter and improve the treatment efficiency, electroflocculation/oxidation is used as the premembrane treatment method. The membrane specific flux attenuation characteristics was compared and analyzed under the conditions of direct ultrafiltration and electroflocculation/oxidation-ultrafiltration. Combined with the analysis of the reversibility of membrane fouling, the mechanism of electroflocculation/oxidation pretreatment to alleviate ultrafiltration membrane fouling was evaluated, and the membrane pore clogging model was used to fit the fouling law. The results show that, in the continuously fed filtration experiment, the electroflocculation/oxidation process involved in the pretreatment and the direct ultrafiltration membrane filtration decreased the ultrafiltration membrane flux to 79.1% and 28.5%, respectively. The reversible resistance generated by ultrafiltration and electroflocculation/oxidation-ultrafiltration processes accounted for 37.70% and 62.26% of their total pollution resistance, whereas the irreversible resistance generated accounted for 47.30% and 12.40%, respectively. Meanwhile, the direct correlation between the the flux dropped and complete clogging became less than that of the ultrafiltration process. The pretreatment significantly strengthened irreversible fouling resistance of the membrane pores. The membrane permeation flux was significantly increased after the electroflocculation/oxidation pretreatment. HIGHLIGHTS The proportion of reversible pollution via EC/O-UF dropped from 62.26% to 37.70%.; The proportion of irreversible pollution via EC/O-UF dropped from 47.30% to 12.40%.; With EC/O, the membrane flux increased from 28.5% to 79.1% after 3 h operation.;

Parkinson’s disease (PD) is a neurodegenerative disorder characterized mainly by motor-related impairment, an accurate, quantitative, and objective diagnosis is an effective way to slow the disease deterioration process. In this paper, a user-friendly auxiliary diagnostic system for PD is constructed based on the upper limb movement conditions of 100 subjects consisting of 50 PD patients and 50 healthy subjects. This system includes wearable sensors that collect upper limb movement data, host computer for data processing and classification, and graphic user interface (GUI). The genetic algorithm optimized random forest classifier is introduced to classify PD and normal states based on the selected optimal features, and the 50 trials leave-one-out cross-validation is used to evaluate the performance of the classifier, with the highest accuracy of 94.4%. The classification accuracy among different upper limb movement tasks and with the different number of sensors are compared, results show that the task with only alternation hand movement also has satisfactory classification accuracy, and sensors on both wrists performance better than one sensor on a single wrist. The utility of the proposed system is illustrated by neurologists with a deployed GUI during the clinical inquiry, opening the possibility for a wide range of applications in the auxiliary diagnosis of PD.

Ecological security patterns (ESPs) provide a solution for balancing the conflicts between ecological conservation and socio-economic development and maintaining sustainable regional development. Identifying sustainable ESPs should be a matter given attention to in order to meet future urban expansion needs. Based on multi-source eco-environmental datasets and remote sensing (RS) containing the history of land-use patterns, our study incorporated future land-use patterns into the ESP identification framework to reduce the potential impact of future urban expansion on the identified ESPs (i.e., ecological corridors and nodes) and to reserve space for future urban development from an urban development perspective. Considering the Changsha–Zhuzhou–Xiangtan (CZX) urban agglomeration, the results show that 57 corridors are extracted, within which 36 key corridors are mainly distributed in the Lukou and Wangcheng districts and Xiangtan and Changsha counties; an additional 21 potential corridors are mainly distributed in the urban built-up area and these corridors connect to Xiangjiang River or its tributary. In addition, 18 pinch points were identified, mainly located adjacent to the Xiangjiang River, Liuyang River, and Laodao River; 9 barrier points are distributed at the junctions of the main roads. A comparison of ESP identification with and without simulated land-use patterns showed the incorporation of future land-use patterns favoured sustainable ESP construction. Furthermore, we discuss the rationality and application of ESP identification from an urban development perspective and emphasize the trade-off between future land-use patterns and ecological conservation, better reflecting the forward-looking thinking of spatial planning.

The forward osmosis (FO) membrane exhibits great performance degradation when contacting with chlorine solutions. The damage of chlorine to membrane material will seriously reduce the lifetime of the membrane and increase the cost of membrane treatment technology. Here, we prepared chlorine-stable membranes by a covalent modification method with cyclohexylamine. The cyclohexylamine observably changed the surface morphology, the roughness (arithmetic average) of the membrane decreased from 22 to 17.2 nm. The addition of cyclohexylamine produced a denser sacrificial layer of short chain polyamide, which made modified membranes possess significantly better chlorine resistance with slightly declined water flux. The water flux of the optimal modified membrane was 10.78 Lm−2 h−1, only 13% less than that of the pristine membrane. Importantly, after 20,000 ppm·h chlorine exposure, the membrane with 1.5 wt% cyclohexylamine had a salt rejection of 77.2% and showed 26.0% lower water flux than pristine TFC (thin film composite) membrane in FO mode. Notably, the grafting membranes could maintain a high performance under acidic chlorination conditions. The membrane with best performance had a salt rejection of 81.6%, exhibiting 24.4% higher salt rejection than pristine membrane with 20,000 ppm·h chlorine exposure at a pH of 4. The cyclohexylamine endowed the FO membrane with better chlorine resistance, making it attractive for the development of chlorine-resistant membrane for environmental and desalination processes. HIGHLIGHTS The addition of cyclohexylamine produced a chlorine-resistant sacrificial layer.; The 1.0 wt% addition of cyclohexylamine did not significantly decrease the water flux of the forward osmosis membrane.; Under acidic conditions, cyclohexylamine could still significantly improve the chlorine resistance of forward osmosis membranes.;

Abstract The integration of HBV DNA into the human genome can disrupt its structure in hepatocellular carcinoma (HCC), but the complexity of HBV genomic integration remains elusive. Here we applied long-read sequencing to precisely elucidate the HBV integration pattern in the human hepatocellular genome. The DNA library was sequenced using the long-read sequencing on GridION and PacBio Sequel II, respectively. The DNA and mRNA were sequenced using next-generation sequencing on Illumina NextSeq. BLAST (Basic Local Alignment Search Tool) and local scripts were used to analyze HBV integration patterns. We established an analytical strategy based on the long-read sequences, and analyzed the complexity of HBV DNA integration into the hepatocellular genome. A total of 88 integrated breakpoints were identified. HBV DNA integration into human genomic DNA was mainly fragmented with different orientations, rarely with a complete genome. The same HBV integration breakpoints were identified among the three platforms. Most breakpoints were observed at P, X, and S genes in the HBV genome, and observed at introns, intergenic sequences, and exons in the human genome. Tumor tissue harbored a much higher integrated number than the adjacent tissue, and the distribution of HBV integrated into human chromosomes was more concentrated. HBV integration shows different patterns between cancer cells and adjacent normal cells. We for the first time obtained the entire HBV integration pattern through long-read sequencing and demonstrated the value of long-read sequencing in detecting the genomic integration structures of viruses in host cells.

As a tool for modifying the genome, gene editing technology has developed rapidly in recent years, especially in the past two years. With the emergence of new gene editing technologies, such as transposon editing tools, numerous advancements have been made including precise editing of the genome, double base editing, and pilot editing. This report focuses on the development of gene editing tools in recent years, elaborates the progress made in classic editing tools, base editor and other new editing tools, and provides insights into challenges and opportunities.

Background: Immune checkpoint inhibitors combined chemotherapy (ICIC) are widely used for various types of lung cancer in the past decade. However, ICIC related adverse events (AEs) are more serious than immune-related adverse events (irAE) or cytotoxic chemotherapy alone.Objective: This prospective interventional study aimed to evaluate the impact of the pharmaceutical care program in reducing adverse events and analyze pharmacy interventions in patients with NSCLC who receive ICIC therapies.Method: NSCLC patients were enrolled in this study, the pharmaceutical care program was introduced after patients received the second cycle ICIC therapies, and were followed by the pharmacist for 6 months after hospital discharge. The percentages of adverse events between patients in and after the first two cycles were analyzed and compared.Results: After the first two treatment cycles, the clinical pharmacist proposed 67 interventions in 30 patients. The most frequent types of intervention were drug discontinuation (40.3%, 27/67) followed by drug modification (14.9%, 10/67). There were significant decreases in AEs after the second cycle with respect to nausea (≥grade-2, 14% vs. 28.3%, p = 0.039), constipation (≥grade-2, 8.8% vs. 21.7%, p = 0.039), diarrhea (≥grade-2, 6% vs. 16.7%, p = 0.031), and myelosuppression (≥grade-2, 15.8% vs. 30.0%, p = 0.022).Conclusion: Provision of pharmaceutical care for NSCLC patients receiving ICIC therapies can optimize drug therapy and reduce adverse events.

Biliary tract cancer (BTC) is a highly aggressive malignant tumor. Serum microRNAs (ser-miRNAs) serve as noninvasive biomarkers to identify high risk individuals, thereby facilitating the design of precision therapies. The study is to prioritize key synergistic ser-miRNAs for the diagnosis of early BTC. Sampling technology, significant analysis of microarrays, Pearson Correlation Coefficients, t-test, decision tree, and entropy weight were integrated to develop a global optimization algorithm of decision forest. The source code is available at https://github.com/SuFei-lab/GOADF.git. Four key synergistic ser-miRNAs were prioritized and the synergistic classification performance was better than the single miRNA’ s. In the internal feature evaluation dataset, the area under the receiver operating characteristic curve (AUC) for each single miRNA was 0.8413 (hsa-let-7c-5p), 0.7143 (hsa-miR-16-5p), 0.8571 (hsa-miR-17-5p), and 0.9365 (hsa-miR-26a-5p), respectively, whereas the synergistic AUC value increased to 1.0000. In the internal test dataset, the single AUC was 0.6500, 0.5125, 0.6750, and 0.7500, whereas the synergistic AUC increased to 0.8375. In the independent test dataset, the single AUC was 0.7280, 0.8313, 0.8957, and 0.8303, and the synergistic AUC was 0.9110 for discriminating between BTC patients and healthy controls. The AUC for discriminating BTC from pancreatic cancer was 0.9000. Hsa-miR-26a-5p was a predictor of prognosis, patients with high expression had shorter survival than those with low expression. In conclusion, hsa-let-7c-5p, hsa-miR-16-5p, hsa-miR-17-5p, and hsa-miR-26a-5p may act as key synergistic biomarkers and provide important molecular mechanisms that contribute to pathogenesis of BTC.

Osteoarthritis (OA) is the most prevalent type of degenerative joint disease; it is reported to be associated with inflammatory responses, chondrocyte apoptosis, and cartilage degeneration. XMU-MP-1 is a selective MST1/2 inhibitor which activates the downstream effector YAP and promotes cell growth. It has displayed excellent benefits in mouse intestinal repair, as well as liver repair and regeneration. However, the effects of XMU-MP-1 on OA remain unclear. In this study, we investigated the therapeutic role of XMU-MP-1 on interleukin-1β (IL-1β)-induced inflammation in mice chondrocytes and the destabilization of the medial meniscus surgery (DMM)-induced OA model. In chondrocytes, treatment with XMU-MP-1 elevated the matrix metalloproteinases (Mmp3, Mmp13) and decreased the extracellular matrix (Col2, Acan) induced by IL-1β. Moreover, XMU-MP-1 strongly inhibited IL-1β-induced chondrocyte apoptosis and significantly promoted chondrocyte proliferation. Furthermore, XMU-MP-1 demonstrated a protective and therapeutic influence on the mouse OA model. These findings indicate that XMU-MP-1 may have a protective effect on cartilage degradation and may be a new potential therapeutic option for OA.

The development of remote sensing technology largely reflects the scientific research level of a country or region. Given that the quantity and quality of research works are important indicators for scientific prowess evaluation, exploratory spatial data analysis and scientometric analysis of remote sensing work published from 2012 to 2021 were performed in this study, utilizing the Web of Sciences database. This study probed the spatial distribution and spatiotemporal evolution at the country/regional level to reveal the spatiotemporal characteristics of knowledge spillover in remote sensing. According to the results, the global spatial distribution of research output in remote sensing presented a significant dispersion; the United States and China were the most active countries. During the study period, Transferring Deep Convolutional Neural Networks for the Scene Classification of High-Resolution Remote Sensing Imagery was one of the most influential studies, both in the field of remote sensing and in the whole scientific community. With respect to the spatial evolution of research output in remote sensing, the gap between continents and the regional imbalance showed a downward trend, while Asia ranked first in the intracontinental disparity and Europe ranked last. For relevant countries/regions and institutions trying to optimize the spatial allocation of scientific and technological resources to narrow regional disparities, this study provides fundamental data and decision-making references.

Abstract Interstitial cystitis/bladder pain syndrome (IC/BPS) has a significant impact on quality of life, but the etiopathogenesis remains largely unknown. The bladder microenvironment of patients with IC/BPS to obtain biological evidence supporting diagnosis and novel therapy is systematically characterized. Single‐cell RNA sequencing (scRNA‐seq) and image mass cytometry (IMC) are applied to bladder biopsies of the IC/BPS cohort. A total of 42 distinct cell clusters are identified from different groups. The increased hyperactivated Th1‐biased response, but not Th2‐biased response, and decreased immunosuppressive Treg are elucidated in the bladder microenvironment of non‐Hunner‐type IC (NHIC)/Hunner‐type IC (HIC). M2/M2‐like macrophage extends in the HIC and M1‐like macrophage extends in NHIC, all of which secrete a range of chemokines with different pattern. The pro‐inflammatory mediators, TNF‐α, produced by tissue‐resident macrophages and IL6, by the inflammatory fibroblasts are identified as key mediators of IC/BPS pathogenesis. Additionally, a regulatory network between different cell types is observed as a shift from structural cell communication in unaffected normal bladder to a Macrophage‐Endothelial‐dominated interactome in NHIC/HIC. The results demonstrate the high heterogeneity in NHIC/HIC, and provide an essential resource for diagnosis, and treatment of IC/BPS in the future by highlighting the importance of the microenvironment of bladder mucosa.

ABSTRACT While circulating cell-free DNA (cfDNA) is becoming a powerful marker for noninvasive identification of infectious pathogens in liquid biopsy specimens, a microbial cfDNA baseline in healthy individuals is urgently needed for the proper interpretation of microbial cfDNA sequencing results in clinical metagenomics. Because noninvasive prenatal testing (NIPT) shares many similarities with the sequencing protocol of metagenomics, we utilized the standard low-pass whole-genome-sequencing-based NIPT to establish a microbial cfDNA baseline in healthy people. Sequencing data from a total of 107,763 peripheral blood samples of healthy pregnant women undergoing NIPT screening were retrospectively collected and reanalyzed for microbiome DNA screening. It was found that more than 95% of exogenous cfDNA was from bacteria, 3% from eukaryotes, and 0.4% from viruses, indicating the gut/environment origins of many microorganisms. Overall and regional abundance patterns were well illustrated, with huge regional diversity and complexity, and unique interspecies and symbiotic relationships were observed for TORCH organisms (Toxoplasma gondii, others [Treponema pallidum {causing syphilis}, hepatitis B virus {HBV}, and human parvovirus B19 {HPV-B19}], rubella virus, cytomegalovirus [CMV], and herpes simplex virus [HSV]) and another common virus, Epstein-Barr virus (EBV). To sum up, our study revealed the complexity of the baseline circulating microbial cfDNA and showed that microbial cfDNA sequencing results need to be interpreted in a more comprehensive manner. IMPORTANCE While circulating cell-free DNA (cfDNA) has been becoming a powerful marker for noninvasive identification of infectious pathogens in liquid biopsy specimens, a baseline for microbial cfDNA in healthy individuals is urgently needed for the proper interpretation of microbial cfDNA sequencing results in clinical metagenomics. Standard low-pass whole-genome-sequencing-based NIPT shares many similarities with the sequencing protocol for metagenomics and could provide a microbial cfDNA baseline in healthy people; thus, a reference cfDNA data set of the human microbiome was established with sequencing data from a total of 107,763 peripheral blood samples of healthy pregnant women undergoing NIPT screening. Our study revealed the complexity of circulating microbial cfDNA and indicated that microbial cfDNA sequencing results need to be interpreted in a more comprehensive manner, especially with regard to geographic patterns and coexistence networks.